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Background: In January 2021, the Commonwealth of Massachusetts granted nurse practitioners (NPs) full practice authority (FPA). Little is known about how care delivery changed after FPA legislation., Purpose: To understand the NP perception of early implementation of FPA in Massachusetts., Methods: Qualitative descriptive design using inductive thematic analysis of open-ended responses to a web-based survey of NPs in Massachusetts from October to December 2021., Findings: Survey response rate was 50.3% (N = 144). Inductive thematic analysis of open-ended responses identified four themes, including: (a) internal and external barriers obstructed FPA implementation, (b) employer communication about scope-of-practice changes was minimal, (c) NPs led initiatives to implement FPA, and (d) some efforts effectively implemented FPA., Discussion: Almost 1 year after FPA was passed, external policies persisted that financially incentivized employers to not change NP scope-of-practice. Concerted efforts are needed to ensure that federal and payer policies, such as incident-to billing, are aligned with state law to encourage the implementation of FPA., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to examine the relationship between nurse practitioner (NP) organizational climate and the implementation of full practice authority (FPA) for NPs., Background: In 2021, Massachusetts passed FPA for NPs. Most NPs did not experience changes to their practice. It is unknown whether NP organizational climate impacts implementation of FPA., Methods: A Web-based survey was distributed to NPs in Massachusetts., Results: Response rate was 50.3% (N = 147). Practice remained unchanged for most. Organizations with more favorable climates experienced more rapid implementation of FPA, resulting in improved efficiency (P = 0.049) and timeliness (P = 0.007) of care. Nurse practitioners outside hospital systems were more likely to report favorable organizational climates and positive change to their practice after FPA., Conclusions: Organizations that facilitate implementation of FPA are likely to experience improvement in efficiency and timeliness of patient care. Nursing leadership, especially within hospital-based organizations, can help achieve these benefits by improving the organizational climate for NPs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The primary care (PC) physician workforce has consistently been projected as requiring additional numbers to meet the needs of the U.S. The Health Resources and Service Administration (HRSA) has reported the PC nurse practitioner (NP) workforce to be 90,000 NPs more than required to meet the PC needs of the U.S. With both clinician types contributing to the PC workforce in the country, it is difficult to understand such an oversupply of NPs with continued deficit in PC physicians. The purpose of this study was to investigate results and methods used for HRSAs current PC workforce projections and compare those with the same used for Bureau of Labor Statistics (BLS) and American Association of Medical Colleges (AAMC) projections. Methods included a review of technical documents, dashboards, and published reports. Interviews with subject matter experts were also completed. Projections were found to differ significantly, as did data and assumptions. Two of the three projections modeled physicians as the sole provider of PC. An integrated model gives the most comprehensive and accurate picture of PC workforce needs. The utilization of NPs as PC providers has been demonstrated to be safe and effective, with the potential to alleviate predicted shortages, improve patient care outcomes, reduce cost, and address PC inequities. Implications include improving workforce data, creating projections that mirror clinical integration in PC, adjusting workforce preparation funding, incentivizing interprofessional collaboration in research, addressing barriers to practice among non-physician providers, and leveraging growth in the NP workforce., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In January 2021, Massachusetts granted nurse practitioners (NPs) full-practice authority (FPA). Little is known about how FPA changes the day-to-day work of NPs., Purpose: To examine changes in practice barriers and care delivery in the early stages of FPA., Methodology: Descriptive analysis of a web-based survey of clinically active NPs in Massachusetts from October to December 2021, using Fisher exact tests to examine the associations between the perception that FPA improved work and other variables., Results: Survey response rate was 50.3% ( N = 147). Overall, 79% of NPs believe that clinical work is unchanged by FPA. Practicing outside institutions is a significant predictor of FPA improving work ( p < .05). Larger proportions of respondents feel that efficiency (22%), patient centeredness (20%), and timeliness (20%) are improved by FPA compared with effectiveness (16%), equity (14%), and safety (10%). Almost half of those reporting that FPA improves overall care also report improved efficiency (50%, p < .0001), but only 22% report improved safety ( p < .05). Of those believing that FPA improved work, a minority no longer need physician review of new controlled substance prescriptions (29%, p < .01), a practice agreement (32%, p < .05), or physician signature on clinical documentation (22%, p < .05)., Conclusions: Almost 1 year after FPA was passed in Massachusetts, the large majority of NPs report no changes in their day-to-day work, suggesting that FPA implementation is slow., Implications: Concerted efforts by regulators, employers, and individual NPs are needed to ensure that legislated FPA is effectively implemented inside organizations and among payers., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2023 American Association of Nurse Practitioners.)

Chimeric fusion transcription factors are oncogenic hallmarks of several devastating cancer entities including pediatric sarcomas, such as Ewing sarcoma (EwS) and alveolar rhabdomyosarcoma (ARMS). Despite their exquisite specificity, these driver oncogenes have been considered largely undruggable due to their lack of enzymatic activity.Here, we show in the EwS model that - capitalizing on neomorphic DNA-binding preferences - the addiction to the respective fusion transcription factor EWSR1-FLI1 can be leveraged to express therapeutic genes.We genetically engineered a de novo enhancer-based, synthetic and highly potent expression cassette that can elicit EWSR1-FLI1-dependent expression of a therapeutic payload as evidenced by episomal and CRISPR-edited genomic reporter assays. Combining in silico screens and immunohistochemistry, we identified GPR64 as a highly specific cell surface antigen for targeted transduction strategies in EwS. Functional experiments demonstrated that anti-GPR64-pseudotyped lentivirus harboring our expression cassette can specifically transduce EwS cells to promote the expression of viral thymidine kinase sensitizing EwS for treatment to otherwise relatively non-toxic (Val)ganciclovir and leading to strong anti-tumorigenic, but no adverse effects in vivo. Further, we prove that similar vector designs can be applied in PAX3-FOXO1-driven ARMS, and to express immunomodulatory cytokines, such as IL-15 and XCL1, in tumor entities typically considered to be immunologically 'cold'.Collectively, these results generated in pediatric sarcomas indicate that exploiting, rather than suppressing, the neomorphic functions of chimeric transcription factors may open inroads to innovative and personalized therapies, and that our highly versatile approach may be translatable to other cancers addicted to oncogenic transcription factors with unique DNA-binding properties., (© 2022. The Author(s).)

Originally applied on domestic and lab animals, assisted reproduction technologies (ARTs) have also found application in conservation breeding programs, where they can make the genetic management of populations more efficient, and increase the number of individuals per generation. However, their application in wildlife conservation opens up new ethical scenarios that have not yet been fully explored. This study presents a frame for the ethical analysis of the application of ART procedures in conservation based on the Ethical Matrix (EM), and discusses a specific case study-ovum pick-up (OPU) procedures performed in the current conservation efforts for the northern white rhinoceros ( Ceratotherium simum cottoni )-providing a template for the assessment of ART procedures in projects involving other endangered species., Competing Interests: CG, GL, and SC were employed by company Avantea. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Biasetti, Hildebrandt, Göritz, Hermes, Holtze, Galli, Lazzari, Colleoni, Pollastri, Spiriti, Stejskal, Seet, Zwilling, Ngulu, Mutisya, Kariuki, Lokolool, Omondo, Ndeereh and de Mori.)

Assisted reproductive technologies (ARTs) can make a difference in biodiversity conservation. Their application, however, can create risks and raise ethical issues that need addressing. Unfortunately, there is a lack of attention to the topic in the scientific literature and, to our knowledge, there is no tool for the ethical assessment of ARTs in the context of conservation that has been described. This paper reports the first applications of the Ethical Assessment Tool (ETHAS) to trans-rectal ovum pick-up (OPU) and in vitro fertilization (IVF) procedures used in a northern white rhinoceros ( Ceratotherium simum cottoni ) conservation project. The ETHAS consists of two checklists, the Ethical Evaluation Sheet and the Ethical Risk Assessment, and is specifically customized for each ART procedure. It provides an integrated, multilevel and standardized self-assessment of the procedure under scrutiny, generating an ethical acceptability ranking (totally, partially, not acceptable) and a risk rank (low, medium, high), and, hence, allows for implementing measures to address or manage issues beforehand. The application of the ETHAS to the procedures performed on the northern white rhinoceros was effective in ensuring a high standard of procedures, contributing to the acceptability and improved communication among the project's partners. In turn, the tool itself was also refined through an iterative consultation process between experts and stakeholders.

Modified vaccinia virus Ankara (MVA) was generated by serial passaging in chicken embryo fibroblasts. During this attenuation, MVA lost the capacity to productively grow in human and most other mammalian cell lines, as well as acquiring a multitude of deletions and mutations in the MVA genome. This means that the precise molecular basis for the MVA host-range restriction is still unknown. The vaccinia virus (VACV) genes F11L and K1L are mutated or truncated in MVA. F11L was previously implicated in VACV-induced cell motility and virion maturation. Here, we demonstrate that the restoration of F11L gene expression in MVA rescued virus-induced cell motility, but had no impact on MVA virion maturation and host-range restriction. Additional insertion of the K1L gene, which restores MVA replication in RK-13 cells, was not sufficient to extend MVA growth capacity to other mammalian cells.

Vaccinia virus (VACV) infection induces phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha), which inhibits cellular and viral protein synthesis. In turn, VACV has evolved the capacity to antagonize this antiviral response by expressing the viral host-range proteins K3 and E3. This study revealed that the host-range genes K1L and C7L also prevent eIF2alpha phosphorylation in modified VACV Ankara (MVA) infection of several human and murine cell lines. Moreover, C7L-deleted MVA (MVA-DeltaC7L) lacked late gene expression, which could be rescued by the function of host-range factor K1 or C7. It was demonstrated that viral gene expression was blocked after viral DNA replication and that it was independent of apoptosis induction. Furthermore, it was found that eIF2alpha phosphorylation in MVA-DeltaC7L-infected cells is mediated by protein kinase R (PKR) as shown in murine embryonic fibroblasts lacking PKR function, and it was shown that this was not due to reduced E3L gene expression. The block of eIF2alpha phosphorylation by C7 could be complemented by K1 in cells infected with MVA-DeltaC7L encoding a reinserted K1L gene (MVA-DeltaC7L-K1L). Importantly, these data illustrated that eIF2alpha phosphorylation by PKR is not responsible for the block of late viral gene expression. This suggests that other mechanisms targeted by C7 and K1 are essential for completing the MVA gene expression cycle and probably also for VACV replication in a diverse set of cell types.

During the French-Soviet space mission "Aragatz," the experiment CIRCE (Compteur Integrateur de Rayonnement Complexe dans l'Espace) recorded the dose rate and quality factor values inside the MIR station. This paper presents results obtained with a new active dose equivalent meter based on microdosimetric techniques and using a low pressure tissue equivalent proportional counter. In terms of lineal energy CIRCE device works in the 0.2-1200 keV micrometer-1 range in tissue. Preliminary studies were performed in photon, neutron and heavy ion beams, and in the real stratosphere cosmic radiation field. Long term measurements on-board MIR station from December 1988 to April 1989 gave an average quality factor value equal to 1.9 +/- 0.3. Through the South Atlantic Anomaly (SAA), the quality factor was equal to 1.4. The temporal orbital variations of the dose rates and quality factors have been established in space dosimetry for the first time.